A three-year study will be conducted to determine the prevalence of metabolic and immunologic indices of islet cell damage and/or glucose intolerance in a cohort of adolescent children with rubella embryopathy in relation to the maternal and offspring HLA phenotypes. The study will thus exploit the naturally occurring paradigm of isletopathy in 6,000 children with congenital rubella who were born during the 1964-65 pandemic to test the general hypothesis that diabetes can arise from a gentically determined adverse host response to viral infection either in the affected individual or in the mother during pregnancy. The study will further define the rubella syndrome and could lead to the identification of specific maternal factors that are of importance in the etiology diabetes and birth defects. Longitidinal observations of blood glucose and insulin response to a standard oral glucose challenge will be obtained along with C-peptide assays, insulin antibody determinations, Hb Alc measurements and screening for auto-antibodies to islet cells and other tissues. These studies, along with HLA typing, will permit an accurate characterization of the type of juvenile diabetes that occurs in the rubella syndrome as well as providing evidence as to whether immunologic abnormalities can precede or only follow the onset of glucose intolerance in this high-risk population.